【摘要】 目的 探究中药丹参有效成分在治疗硅肺中的作用和作用机制。方法 运用网络药理学和分子对接技术筛选出中药丹参治疗硅肺的有效成分和关键靶点。热转移实验检测有效成分与关键靶点的结合稳定性，细胞划痕实验检测上皮细胞的迁移能力，蛋白质印迹法检测上皮间质转化的标志蛋白、纤维化标志蛋白以及凋亡相关蛋白的表达水平。结果 中药丹参的有效成分木犀草素与硅肺关键靶点B淋巴细胞瘤-2 (BCL-2)具有最低的结合能，热转移实验验证木犀草素与BCL-2蛋白具有较好的结合稳定性。细胞划痕实验显示木犀草素能够抑制转化生长因子-β1刺激的上皮细胞迁移。蛋白质印迹法证明木犀草素能够抑制BCL-2蛋白的表达，与转化生长因子-β1刺激组相比，木犀草素给药及沉默BCL-2后能够抑制上皮间质转化及胶原蛋白的形成，进而抑制纤维化的进程。木犀草素给药及沉默BCL-2后能够促进细胞凋亡。结论 木犀草素能够与BCL-2结合进而抑制硅肺纤维化的进程，其作用机制可能与木犀草素能够促进细胞凋亡有关。更多还原

【Abstract】 Objective To explore the potential and mechanism of the active components of the traditional Chinese medicine Salvia miltiorrhiza(Danshen) in the treatment of silicosis. Methods Network pharmacology and molecular docking approaches were employed to identify the bioactive constituents and critical molecular targets of Danshen for its therapeutic potential in teating silicosis. The cellular thermal shift assay was used to test the binding stability of the effective components with key targets, cell scratch assays were used to test the migration ability of epithelial cells, and Western Blotting analysis was conducted to quantify the expression profiles of markers indicative of epithelial-mesenchymal transition, fibrosis and proteins associated with apoptosis. Results Network pharmacology and molecular docking identified luteolin, an effective component of Danshen, as having the lowest binding energy with the key silicosis target B cell lymphoma-2(BCL-2).Subsequently, cellular thermal shift assay experiments confirmed that luteolin had a good binding stability with BCL-2 protein. Phenotypically, cell scratch assays showed that luteolin could inhibit the migration of epithelial cells stimulated by transforming growth factor-β1. Western Blotting experiments demonstrated that luteolin could inhibit the expression of BCL-2 protein, and, compared to the transforming growth factor-β1stimulation group, luteolin administration and BCL-2 silencing could inhibit epithelial-mesenchymal transition and collagen formation, thereby inhibiting the progression of fibrosis. Mechanistically, luteolin administration and BCL-2 silencing could promote apoptosis. Conclusion Luteolin can bind to BCL-2 and inhibit the progression of silicosis fibrosis, and its mechanism of action may be related to its ability to promote apoptosis.更多还原